Differential meta-analysis of RNA-seq data from multiple studies

TL;DR

This paper explores the use of p-value combination techniques for meta-analysis of RNA-seq data from multiple studies, demonstrating their effectiveness over traditional models especially with high inter-study variability.

Contribution

It introduces the application of p-value combination methods to RNA-seq meta-analysis and compares their performance to a generalized linear model with study effects.

Findings

Meta-analysis methods outperform GLM with study effect in high variability scenarios.

P-value combination techniques effectively account for biological and technical variability.

The R package metaRNASeq facilitates implementation of these methods.

Abstract

High-throughput sequencing is now regularly used for studies of the transcriptome (RNA-seq), particularly for comparisons among experimental conditions. For the time being, a limited number of biological replicates are typically considered in such experiments, leading to low detection power for differential expression. As their cost continues to decrease, it is likely that additional follow-up studies will be conducted to re-address the same biological question. We demonstrate how p-value combination techniques previously used for microarray meta-analyses can be used for the differential analysis of RNA-seq data from multiple related studies. These techniques are compared to a negative binomial generalized linear model (GLM) including a fixed study effect on simulated data and real data on human melanoma cell lines. The GLM with fixed study effect performed well for low inter-study variation and small numbers of studies, but was outperformed by the meta-analysis methods for moderate to large inter-study variability and larger numbers of studies. To conclude, the p-value combination techniques illustrated here are a valuable tool to perform differential meta-analyses of RNA-seq data by appropriately accounting for biological and technical variability within studies as well as additional study-specific effects. An R package metaRNASeq is available on the R Forge.